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Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.
Catheter ablation is a safe and effective therapy for the treatment of supraventricular tachycardia in children. Current improvements in technology have allowed progressive reduction in radiation exposure associated with the procedure. To assess the impact of three-dimensional mapping, we compared acute procedural results collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to published results from the Prospective Assessment after Pediatric Cardiac Ablation study.
Inclusion and exclusion criteria from the Prospective Assessment after Pediatric Cardiac Ablation study were used as guidelines to select patient data from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to compare acute procedural outcomes between cohorts. Outcomes assessed include procedural and fluoroscopy exposure times, success rates of procedure, and complications.
In 786 ablation procedures, targeting 498 accessory pathways and 288 atrioventricular nodal reentrant tachycardia substrates, average procedural time (156.5 versus 206.7 minutes, p < 0.01), and fluoroscopy time (1.2 versus 38.3 minutes, p < 0.01) were significantly shorter in the study group. Success rates for the various substrates were similar except for manifest accessory pathways which had a significantly higher success rate in the study group (96.4% versus 93.0%, p < 0.01). Major complication rates were significantly lower in the study group (0.3% versus 1.6%, p < 0.01).
In a large, multicentre study, three-dimensional systems show favourable improvements in clinical outcomes in children undergoing catheter ablation of supraventricular tachycardia compared to the traditional fluoroscopic approach. Further improvements are anticipated as technology advances.
Sleep and circadian timing shifts later during adolescence, conflicting with early school start times, and resulting in circadian misalignment. Although circadian misalignment has been linked to depression, substance use, and altered reward function, a paucity of experimental studies precludes the determination of causality. Here we tested, for the first time, whether experimentally-imposed circadian misalignment alters the neural response to monetary reward and/or response inhibition.
Healthy adolescents (n = 25, ages 13–17) completed two in-lab sleep schedules in counterbalanced order: An ‘aligned’ condition based on typical summer sleep-wake times (0000–0930) and a ‘misaligned’ condition mimicking earlier school year sleep-wake times (2000–0530). Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward (morning only) and response inhibition (morning and afternoon) tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively.
Bilateral ventral striatal (VS) activation during reward outcome was lower during the Misaligned condition after accounting for the prior night's total sleep time. Bilateral VS activation during reward anticipation was lower during the Misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the Misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan.
Our findings provide novel experimental evidence that circadian misalignment analogous to that resulting from school schedules may have measurable impacts on healthy adolescents' reward processing and inhibition of prepotent responses.
Social anxiety disorder (SAD) is common. It usually starts in adolescence, and without treatment can disrupt key developmental milestones. Existing generic treatments are less effective for young people with SAD than with other anxiety disorders, but an adaptation of an effective adult therapy (CT-SAD-A) has shown promising results for adolescents.
The aim of this study was to conduct a qualitative exploration to contribute towards the evaluation of CT-SAD-A for adoption into Child and Adolescent Mental Health Services (CAMHS).
We used interpretative phenomenological analysis (IPA) to analyse the transcripts of interviews with a sample of six young people, six parents and seven clinicians who were learning the treatment.
Three cross-cutting themes were identified: (i) endorsing the treatment; (ii) finding therapy to be collaborative and active; challenging but helpful; and (iii) navigating change in a complex setting. Young people and parents found the treatment to be useful and acceptable, although simultaneously challenging. This was echoed by the clinicians, with particular reference to integrating CT-SAD-A within community CAMHS settings.
The acceptability of the treatment with young people, their parents and clinicians suggests further work is warranted in order to support its development and implementation within CAMHS settings.
Cognitive therapy, based on the Clark and Wells (1995) model, is a first-line treatment for adults with social anxiety disorder (SAD), and findings from research settings suggest it has promise for use with adolescents (Cognitive Therapy for Social Anxiety Disorder in Adolescents; CT-SAD-A). However, for the treatment to be suitable for delivery in routine clinical care, two questions need to be addressed.
Can therapists be trained to achieve good outcomes in routine Child and Adolescent Mental Health Services (CAMHS), and what are the costs associated with training and treatment?
CAMHS therapists working in two NHS trusts received training in CT-SAD-A. They delivered the treatment to adolescents with SAD during a period of supervised practice. We examined the clinical outcomes for the 12 patients treated during this period, and estimated costs associated with treatment and training.
Treatment produced significant improvements in social anxiety symptoms, general anxiety and depression symptoms, and reductions in putative process measures. Seventy-five per cent (9 out of 12) patients showed a reliable and clinically significant improvement in social anxiety symptoms, and 64% (7/11) lost their primary diagnosis of SAD. The total cost to the NHS of the CT-SAD-A treatment was £4047 (SD = £1003) per adolescent treated, of which £1861 (SD = £358) referred to the specific estimated cost of face-to-face delivery; the remaining cost was for training and supervising therapists who were not previously familiar with the treatment.
This study provides preliminary evidence that clinicians can deliver good patient outcomes for adolescents with SAD in routine CAMHS during a period of supervised practice after receiving a 2-day training workshop. Furthermore, the cost of delivering CT-SAD-A with adolescents appeared to be no more than the cost of delivering CT-SAD with adults.
When presenting with a first episode of psychosis (FEP), migrants can have different demographic and clinical characteristics to the native-born population and this was examined in an Irish Early Intervention for Psychosis service.
All cases of treated FEP from three local mental health services within a defined catchment area were included. Psychotic disorder diagnoses were determined using the SCID and symptom and functioning domains were measured using validated and reliable measures.
From a cohort of 612 people, 21.1% were first-generation migrants and there was no difference in the demographic characteristics, diagnoses, symptoms or functioning between migrants and those born in the Republic of Ireland, except that migrants from Africa presented with less insight. Of those admitted, 48.6% of admissions for migrants were involuntary compared to 37.7% for the native-born population (p = 0.09).
First-generation migrants now make up a significant proportion of people presenting with a FEP to an Irish EI for psychosis service. Broadly the demographic and clinical characteristics of migrants and those born in the Republic of Ireland are similar, except for less insight in migrants from Africa and a trend for a higher proportion of involuntary admissions in the total migrant group.
To examine rural–urban differences in temporal trends and risk of inappropriate antibiotic use by agent and duration among women with uncomplicated urinary tract infection (UTI).
Observational cohort study.
Using the IBM MarketScan Commercial Database (2010–2015), we identified US commercially insured women aged 18–44 years coded for uncomplicated UTI and prescribed an oral antibiotic agent. We classified antibiotic agents and durations as appropriate versus inappropriate based on clinical guidelines. Rural–urban status was defined by residence in a metropolitan statistical area. We used modified Poisson regression to determine the association between rural–urban status and inappropriate antibiotic receipt, accounting for patient- and provider-level characteristics. We used multivariable logistic regression to estimate trends in antibiotic use by rural–urban status.
Of 670,450 women with uncomplicated UTI, a large proportion received antibiotic prescriptions for inappropriate agents (46.7%) or durations (76.1%). Compared to urban women, rural women were more likely to receive prescriptions with inappropriately long durations (adjusted risk ratio 1.10, 95% CI, 1.10–1.10), which was consistent across subgroups. From 2011 to 2015, there was slight decline in the quarterly proportion of patients who received inappropriate agents (48.5% to 43.7%) and durations (78.3% to 73.4%). Rural–urban differences varied over time by agent (duration outcome only), geographic region, and provider specialty.
Inappropriate antibiotic prescribing is quite common for the treatment of uncomplicated UTI. Rural women are more likely to receive inappropriately long antibiotic durations. Antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing and to reduce unnecessary exposure to antibiotics, particularly in rural settings.
Cognitive therapies are developed on the principle that specific cognitive appraisals are key determinants in the development and maintenance of mental health disorders. It is likely that particular appraisals of the coronavirus pandemic will have explanatory power for subsequent mental health outcomes in the general public. To enable testing of this hypothesis we developed a questionnaire assessing coronavirus-related cognitions.
12 285 participants completed online a 46-item pool of cognitions about coronavirus and six measures of different mental health problems. The sample was randomly split into derivation and validation samples. Exploratory factor analyses determined the factor structure, selection of items, and model fit in the derivation sample. Confirmatory factor analysis (CFA) then tested this model in the validation sample. Associations of the questionnaire with mental health outcomes were examined.
The 26-item, seven-factor, Oxford Psychological Investigation of Coronavirus Questionnaire [TOPIC-Q] was developed. CFA demonstrated a good model fit (χ2 = 2108.43, df = 278, p < 0.001, comparative fit index (CFI) = 0.950, Tucker−Lewis index (TLI) = 0.942, root mean square error of approximation (RMSEA) = 0.033, standardized root mean square residual (SRMR) = 0.038). The factors were: cognitions about (1) safety and vulnerability, (2) negative long-term impact, (3) having the virus, (4) spreading the virus, (5) social judgment, (6) negative self, and (7) being targeted. The questionnaire explained significant variance in depression (45.8%), social anxiety (37.3%), agoraphobia (23.2%), paranoia (27.3%), post-traumatic stress disorder (57.1%), and panic disorder (31.4%). Cognitions about negative long-term impact had the greatest explanatory power across disorders.
TOPIC-Q provides a method to assess appraisals of the pandemic, which is likely to prove helpful both in longitudinal studies assessing mental health outcomes and in delivery of psychological therapy.
Structural models of psychopathology consistently identify internalizing (INT) and externalizing (EXT) specific factors as well as a superordinate factor that captures their shared variance, the p factor. Questions remain, however, about the meaning of these data-driven dimensions and the interpretability and distinguishability of the larger nomological networks in which they are embedded.
The sample consisted of 10 645 youth aged 9–10 years participating in the multisite Adolescent Brain and Cognitive Development (ABCD) Study. p, INT, and EXT were modeled using the parent-rated Child Behavior Checklist (CBCL). Patterns of associations were examined with variables drawn from diverse domains including demographics, psychopathology, temperament, family history of substance use and psychopathology, school and family environment, and cognitive ability, using instruments based on youth-, parent-, and teacher-report, and behavioral task performance.
p exhibited a broad pattern of statistically significant associations with risk variables across all domains assessed, including temperament, neurocognition, and social adversity. The specific factors exhibited more domain-specific patterns of associations, with INT exhibiting greater fear/distress and EXT exhibiting greater impulsivity.
In this largest study of hierarchical models of psychopathology to date, we found that p, INT, and EXT exhibit well-differentiated nomological networks that are interpretable in terms of neurocognition, impulsivity, fear/distress, and social adversity. These networks were, in contrast, obscured when relying on the a priori Internalizing and Externalizing dimensions of the CBCL scales. Our findings add to the evidence for the validity of p, INT, and EXT as theoretically and empirically meaningful broad psychopathology liabilities.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments.
A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations.
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Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
Social anxiety disorder (SoAD) in youth is often treated with a generic form of cognitive behavioural therapy (CBT). Some studies have suggested that primary SoAD is associated with lower recovery rates following generic CBT compared with other anxiety disorders.
This systematic review and meta-analysis investigated recovery rates following generic CBT for youth with primary SoAD versus other primary anxiety disorders.
Five databases (PsycINFO, Web of Science, PubMed, Embase, Medline) were searched for randomised controlled trials of generic CBT for child and/or adolescent anxiety.
Ten trials met criteria for inclusion in the systematic review, six of which presented sufficient data for inclusion in the meta-analysis. Sixty-seven did not report data on recovery rates relative to primary diagnosis. While most individual studies included in the systematic review were not sufficiently powered to detect a difference in recovery rates between diagnoses, there was a pattern of lower recovery rates for youth with primary SoAD. Across the trials included in the meta-analysis, the post-CBT recovery rate from primary SoAD (35%) was significantly lower than the recovery rate from other primary anxiety disorders (54%).
Recovery from primary SoAD is significantly less likely than recovery from any other primary anxiety disorder following generic CBT in youth. This suggests a need for research to enhance the efficacy of CBT for youth SoAD.
The mental health of third-level students is of major societal concern with the gap between the demand for services and supports offered at crisis level. In Ireland, similar to elsewhere, colleges have responded to this need in vastly differing ways, with student counselling services available to all institutions, and student health departments and sessional psychiatry in some of the larger institutions, with none operating as a single multidisciplinary service. There is an increasing recognition for a more systematised approach, with the establishment of International Networks, Charters and Frameworks. These advocate for a whole institutional approach to student mental health, in addition to the development of an integrated system of supports with effective pathways to appropriate care. This paper, by members of the Youth and Student Special Interest Group of the College of Psychiatrists of Ireland, contextualises student mental health currently and describes future directions for this emerging field. It is a call to action to develop a structure that supports the needs of students with mental health problems across the full range of the spectrum from mild to severe.
Optical tracking systems typically trade off between astrometric precision and field of view. In this work, we showcase a networked approach to optical tracking using very wide field-of-view imagers that have relatively low astrometric precision on the scheduled OSIRIS-REx slingshot manoeuvre around Earth on 22 Sep 2017. As part of a trajectory designed to get OSIRIS-REx to NEO 101955 Bennu, this flyby event was viewed from 13 remote sensors spread across Australia and New Zealand to promote triangulatable observations. Each observatory in this portable network was constructed to be as lightweight and portable as possible, with hardware based off the successful design of the Desert Fireball Network. Over a 4-h collection window, we gathered 15 439 images of the night sky in the predicted direction of the OSIRIS-REx spacecraft. Using a specially developed streak detection and orbit determination data pipeline, we detected 2 090 line-of-sight observations. Our fitted orbit was determined to be within about 10 km of orbital telemetry along the observed 109 262 km length of OSIRIS-REx trajectory, and thus demonstrating the impressive capability of a networked approach to Space Surveillance and Tracking.
There is a high rate of psychiatric comorbidity in patients with epilepsy. However, the impact of surgical treatment of refractory epilepsy on psychopathology remains under investigation. We aimed to examine the impact of epilepsy surgery on psychopathology and quality of life at 1-year post-surgery in a population of patients with epilepsy refractory to medication.
This study initially assessed 48 patients with refractory epilepsy using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life in Epilepsy Inventory 89 (QOLIE-89) on admission to an Epilepsy Monitoring Unit (EMU) as part of their pre-surgical assessment. These patients were again assessed using the SCID-I, QOLIE-89 and HADS at 1-year follow-up post-surgery.
There was a significant reduction in psychopathology, particularly psychosis, following surgery at 1-year follow-up (p < 0.021). There were no new cases of de novo psychosis and surgery was also associated with a significant improvement in the quality of life scores (p < 0.001).
This study demonstrates the impact of epilepsy surgery on psychopathology and quality of life in a patient population with refractory surgery. The presence of a psychiatric illness should not be a barrier to access surgical treatment.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Through diversity of composition, sequence, and interfacial structure, hybrid materials greatly expand the palette of materials available to access novel functionality. The NSF Division of Materials Research recently supported a workshop (October 17–18, 2019) aiming to (1) identify fundamental questions and potential solutions common to multiple disciplines within the hybrid materials community; (2) initiate interfield collaborations between hybrid materials researchers; and (3) raise awareness in the wider community about experimental toolsets, simulation capabilities, and shared facilities that can accelerate this research. This article reports on the outcomes of the workshop as a basis for cross-community discussion. The interdisciplinary challenges and opportunities are presented, and followed with a discussion of current areas of progress in subdisciplines including hybrid synthesis, functional surfaces, and functional interfaces.